Parkinson Flashcards

1
Q

Parkinson’s

A
Progressive nervous system disease
Starts gradually
Movement disorder
◦ Bradykinesia
◦ Muscle rigidity
◦ Resting tremors
◦ Postural instability
Pathology
◦ Extensive deterioration of neurons within basal ganglia of the brain
◦ Dopamine loss
◦ Increased cholinergic activity
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2
Q

Therapeutic goals

A

◦ Ideal treatment that reverses neuronal degeneration or prevents further
degeneration does not exist
◦ The goal is to improve the patient’s ability to carry out the activities of daily life
◦ Drug selection and dosages are determined by the extent to which PD interferes
with work, dressing, eating, bathing, and other activities of daily living

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3
Q

Therapeutic Drug Class Alternatives

A
Dopaminergics
Dopamine Agonists
MAO B inhibitors
Glutamate antagonist (amantadine)
Anticholinergics
Catechol‐O‐Methyltransferase
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4
Q

Dopaminergics - Options

A

◦ Levodopa (Dopar, Larodopa)
◦ Levodapa‐carbidopa(Sinemet, Sinemet DR, Madopar)
◦ Duodopa (continuous to small intestine)

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5
Q

Dopaminergics clinical indications

A

◦ Most effective for tremors and rigidity

◦ Also used: postencephalitic and PD associated with cerebral ateriosclerosis

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6
Q

Levadopa Pharmacokinetics and

Pharmacodynamics - Conversion

A

Conversion of levodopa to dopamine
◦ Restores normal balance between excitation and inhibition of neurons
◦ Carbifdopa enhances concentration of levodopa to reach brain
Absorption in gut, hampered by food
Biotransformed in liver
Short ½ life, requires frequent dosing
Renally eliminated, breast milk also.

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7
Q

Levadopa SE

A

◦ N&V most common

◦ Other: dry mouth, difficulty swallowing, worsening hand tremors, numbness, syncope, sudden sleep

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8
Q

Levadopa Long Term Therapy

A

◦ Dyskinesia, on‐off phenomenon, psychiatric manifestations, cardiac arrhythmia

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9
Q

Levadopa Contraindications

A

◦ Concurrent MAOIs, uncontrolled HTN, narrow angle glaucoma, malignant melanoma
◦ CVD, Renal, liver disease, PUD, asthma/COPD, adrenergic therapy, Pregnance Cat D, BF, children < 12

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10
Q

Levadopa Prescription and Monitoring

A

Frequency of dosing patient dependent
◦ 75mg carbidopa needed to achieve full decarboxylation
Target dose
◦ Smallest dosage necessary to control symptoms and decrease disability
Monitoring
◦ Periodic CBC, LFTs, renal studies
May interfere with urine glucose and ketone tests

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11
Q

Dopamine Agonists - Options

A
◦ Bromocriptine (Parlodel)  
◦ Pergolide (Permax)
◦ Rotigotine (patch)
◦ Apomorphine (IV/IM) Ropinirole (Requip CR)
◦ Pramipexole (Mirapex)
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12
Q

Dopamine Agonists - Clinical Indications

A

◦ Idiopathic and encephalic PD, restless legs
◦ Adjunct to levodopa
◦ Cannot be discontinued abruptly
◦ Require 3x a day dosing

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13
Q

Dopamine Agonists - PK/PD

A

◦ Pramipexole no hepatic metabolism

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14
Q

Dopamine Agonists SE

A

◦ Orthostatic hypotension, GI disturbance, less dyskinesia, drowsiness, insomnia
◦ Dyspnea, angina, arrhythmias, orthostosis possible (esp. in hot environs), compulsive behaviors

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15
Q

Dopamine Agonists - Interacions

A

Pergolide

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16
Q

Monamine Oxidase B Inhibitors - Options

A

◦ Selegiline (Eldepryl)
◦ Rasegeline (Agilect, Zelipar)
◦ Safinamide

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17
Q

Monamine Oxidase B Inhibitors - Clinical Indications

A

◦ Adjunct to Levodopa

◦ Most effective early stages, early onset

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18
Q

Monamine Oxidase B Inhibitors - MOA

A

◦ Selegiline:
◦ blocks MAO‐B; neuroprotective properties?
◦ May be monotherapy; dose twice daily
◦ Amphetamine metabolites
◦ Rasegiline:
◦ Prolongs survival of dopamine neurons; neuroprotective properties?

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19
Q

Monamine Oxidase B Inhibitors SE

A

Nause, dry mouth, constipation, confusion, hallucinations, lightheadedness, drug/food interactions

20
Q

Monamine Oxidase B Inhibitors - Seleginie

A

◦ Side effects similar to levodopa
◦ Cautious use of doses of 10mg/d
◦ Caution: PUD, arrhythmia, TDK, psychosis

21
Q

Monamine Oxidase B Inhibitors - Rasegiline

A

◦ SE similar to levodopa in combo
◦ May exacerbate dyskinesia
◦ Interactions TCAs. Selegiline: CNS toxicity, death

22
Q

Glutamate Antagonist - Clinical indications

A
◦ Clinical Indications
◦ Limited efficacy, rarely prescribed initially, adjunct
◦ Effects short‐lived and mild
◦ Has stimulatory effect for some
◦ Especially useful if tremors prominent
23
Q

Glutamate Antagonist - MOA

A

◦ Reduces drug‐induced dyskinesias without worsening other symptoms

24
Q

Glutamate Antagonist - SE

A

SE: peripheral edema, skin mottling, confusion; toxic SE more common older adults

25
Q

Anticholinergics - Options

A

◦ Trihexyphenidyl (Broflex, Artane, Agitane)
◦ Benztropine (Cogentin)antipsychotic drug‐induced PD)
◦ Orphenadrine (Disipal)
◦ Procyclidine (Kemadrin, Arpicolin)

26
Q

Anticholinergics - Clinical Inidcations

A

◦ Early in early onset, tremor but little rigidity or bradykinesia, drooling, EPS
◦ Not in older adults or those with dementia; BPH, Closed angle glaucoma

27
Q

Specifics - MOA

A

◦ Inhibit acetylcholine at muscarinic receptors

◦ Restore cholinergic‐dopaminergic balance

28
Q

Specifics - SE

A

◦ Worse in older adults

◦ Dry mouth, constipation, urinary retention, tachycardia,palpitations, impaired sweating

29
Q

Specifics - Interactions

A

◦ Antipsychotics, antihistamines, antidepressants

30
Q

Catechol‐O‐Methyltransferase (COMT) - Options

A

◦ Entacopone (Comtan)

◦ Tolcapone (Tasmar)+

31
Q

Catechol‐O‐Methyltransferase (COMT) - Clinical Indications

A

◦ Adjunct to levodopa

◦ Ineffective when given alone

32
Q

Catechol‐O‐Methyltransferase (COMT) - MOA

A

◦ Higher sustained serum levels of dopamine

33
Q

Catechol‐O‐Methyltransferase (COMT) - SE

A

◦ Due to increased dopaminergic stimulation

◦ Tolcapone: dsykinesia, hallucinations, confusion, N, orthostatic hypotension. Entacopone: N, dyskinesia

34
Q

Therapeutic Goals

A

Ideal treatment that reverses neuronal degeneration or
prevents further degeneration does not exist
The goal is to improve the patient’s ability to carry out
the activities of daily life
Drug selection and dosages are determined by the
extent to which PD interferes with work, dressing,
eating, bathing, and other activities of daily living

35
Q

Management Strategies

A

Consider
◦ Patient age
◦ Signs and symptoms
◦ Stage of Disease
◦ Degree of functional disability
◦ Level of physical activity and productivity
◦ Shared decision‐making
◦ The effect of disease on the dominant hand
◦ The degree to which the disease interferes with work, activities of daily living, or social and leisure function
◦ The presence of significant bradykinesia or gait disturbance
◦ Patient values and preferences regarding the use of medications

36
Q

MAO‐B Inhibitors - Patients at any age

A

◦ Patients at any age with very early PD and minimal signs and symptoms who are looking for a small
amount of benefit

37
Q

Glutamate Antagonists (Amantadine) - fast facts

A

◦ Patients with PD and mild symptoms, particularly when tremor is prominent
◦ Well‐tolerated in younger patients

38
Q

Anticholinergics fast facts

A

◦ Patients with PD who are ≤65 years of age and have disturbing tremor but do not have significant
bradykinesia or gait disturbance
◦ Patients with more advanced disease who have persistent tremor despite treatment with levodopa or
DA

39
Q

Initial Treatment Progressive Disease ≤

65 Years Mild to Moderate

A

Levodopa or levodopa‐carbidopa first line for many
◦ Tailor to individual

Progressive disease usually requires more than monotherapy with dopamine agonist after a few
years
Debate over the potential neuroprotective vs. neurotoxic effects of levodopa remains
unresolved

40
Q

Initial Treatment Progressive Disease >

65 Years Mild to Moderate

A

Levodopa recommended for older adult
◦ DAs are not well tolerated in older adults and those with cognitive dysfunction
◦ Levodopa is more effective for improving motor function and quality of life
Debate over the potential neuroprotective vs. neurotoxic effects of levodopa remains
unresolved

41
Q

Moderate to Severe Disease Any Age

A

Levodopa preferred
◦ L‐dopa main precursor of dopamine synthesis
Most effective drug for symptomatic treatment of PD
Superior effects on:
◦ Motor function
◦ Activities of daily living
◦ Quality of life

42
Q

Titration and Maintenance

A

Titrate up slowly
Maintain levodopa at lowest effective dose
Add adjunct therapy based on age, symptoms
Monitor for side effects
Lower dose of levodopa if side effects increasing
Monitor for drug interactions
Monitor renal and liver status

43
Q

On‐Off Phenomenon

A

A switch between mobility and immobility in levodopa‐treated patients
Occurs as an end of‐dose or “wearing off” worsening of motor function
Or, much less commonly, as sudden and unpredictable motor fluctuations

44
Q

Non‐Motor Symptoms

A
90% of patients develop nonmotor symptoms (e.g., autonomic disturbances, depression, 
dementia, psychosis)
Autonomic symptoms
◦ Constipation, urinary incontinence, drooling, orthostatic hypotension, and cold intolerance
Sleep disturbance
◦ Excessive daytime sleepiness
◦ Periodic limb movements of sleep
◦ Insomnia
45
Q

Parkinsonism‐Hyperpyrexia Syndrome

A

Rare occurrence
Sudden withdrawal or dose reduction of antiparkinson medication
Or when switching from 1 drug to another
◦ Most common drugs: Levodopa, dopamine agonist, rare amantadine
Management
◦ Replace antiparkinson medications
◦ Formuations: oral, NG, IV, infusion, transdermal
Severe symptoms: admit